The receptor-activity-modifying protein (RAMP) family is currently understood to comprise three members (RAMP1, RAMP2, and RAMP3); they are single transmembrane domain proteins that associate with certain G-protein coupled receptors and influence receptor function. For example, RAMPs are required to transport the calcitonin receptor-like receptor (CRLR) to the plasma membrane. The phenotype of the CRLR varies depending upon which RAMP is involved in its transport. For example, RAMP1 transported CRLR exhibits a calcitonin gene-related peptide (CGRP) receptor phenotype, whereas RAMP2 or RAMP3 transported CRLR exhibits an adrenomedullin receptor phenotype (McLatchie et al., Nature 393: 333-339, 1998; Christopoulos et al., Mol. Pharmacol. 56: 235-42,1999). In addition, RAMP1 and RAMP3, but not RAMP-2, also associate with the calcitonin (CT) family of receptors, increasing receptor specificity for amylin (islet amyloid polypeptide) and decreasing specificity for calcitonin (Muff et al., Endocrinology 140: 2924-27, 1999).
Further study is required to understand the complex role of RAMPs in the function of some G-protein coupled receptors and the therapeutic implications associated with these functions. Accordingly, the present invention provides biological tools to study RAMP1, RAMP2, and RAMP3 function and methods to identify agents that regulate these RAMPs for use in treating diseases and conditions that are linked to these functions.